Endorphin analogs with potent and long-lasting analgesic effects

The analgesic effects of intracerebroventricular administration of alpha, gamma, and beta-endorphin and their D-Ala2-analogs were examined in the rat using the tail-flick test. Analgesia was produced by all substances. The actions of D-Ala2-alpha and -beta-endorphin were considerably greater than the parent forms, whereas D-Ala2-gamma-endorphin was approximately equivalent to the parent compound. The marked analgesia was dose dependent and prolonged for all analogs. Since these effects were reversed by the opiate antagonist naloxone, it was concluded that opiate receptors mediate the action of these analogs. It is suggested that these analogs may be useful in behavioral tests when a longer duration of action is desirable.